35180-01-9, These common heterocyclic compound, 35180-01-9, name is Chloromethyl isopropyl carbonate, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
Preparation of Compound 165Compound 165. A 20 mL microwave vial was charged with starting acid (300 mg, 0.632 mmol), potassium carbonate (1 14 mg, 0.822 mmol), sodium iodide (66.3 mg, 18.1 mu, 0.442 mmol), DMF (10 mL) and chloromethyl isopropyl carbonate (116 mg, 0.758 mmol). Heated at 80 C in microwave for 20 min, then the reaction mixture was partitioned between EtOAc and water (80 mL each). The organic layer was separated, washed with water then brine (80 mL each), dried (magnesium sulfate), filtered and concentrated. The resulting residue was purified by MPLC using an Isco Combiflash (40 g column) 0-80% EtOAc in hexanes linear gradient over 24 column volumes at 40 mL/min. Product isolated from column was dissolved in MeCN (10 mL), treated with water (8 mL) then the resulting mixture was frozen and lyophilized. Gave 166 (291 mg, 0.479 mmol, 76%) as a white solid. Analysis carried out by LCMS (60-98% aqueous MeCN, formic acid modifier, 7 min, C4) ESI-MS m/z calc. 590.2662, found 591.59 (M+l)+; Retention time: 2.59 minutes. 1H NMR (300.0 MHz, DMSO) delta 7.27 (s, 1H), 5.84 (dd, J = 6.2, 9.7 Hz, 2H), 4.91 (d, J = 16.7 Hz, 1H), 4.80 (septet, J = 6.2 Hz, 1H), 3.89 (d, J = 16.7 Hz, 1H), 3.55 (br s, 4H), 3.45 – 3.35 (m, 4H), 2.13 – 1.98 (m, 1H), 1.79 – 1.33 (m, 7H), 1.30 (s, 9H), 1.24 (d, J = 6.2 Hz, 6H), 0.77 (d, J = 6.4 Hz, 3H) and 0.75 – 0.57 (m, 2H) ppm.
Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand reaction routes of 35180-01-9.
Reference:
Patent; VERTEX PHARMACEUTICALS INCORPORATED; GREEN, Jeremy; WILSON, Dean, M.; KONG, Laval, Chan Chun; DAS, Sanjoy, Kumar; POISSON, Carl; COURT, John, J.; TANG, Qing; LI, Pan; COLLIER, Philip, N.; WAAL, Nathan; LAUFFER, David, J.; DORSCH, Warren; WO2012/6055; (2012); A2;,
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